Helen P. Makarenkova, Ph.D.

Research Focus

Muscle development and regeneration

Skeletal muscle atrophy is a devastating disorder that occurs in a large number of chronic diseases such as cancer, diabetes, trauma, cystic fibrosis, HIV, aging and genetic disorders. Research in my laboratory focuses on the mechanisms of muscle regeneration and regulation of satellite cell (muscle progenitor cell) function.

Satellite cells are the resident stem cell of muscle: upon activation they give rise to a proliferating myoblast population that differentiates into myofibres. Recent progress in understanding the muscle regeneration process in complex degeneration models (rather than simple focal injury models) has suggested that disrupted signaling within the microenvironment is a driver of failed regeneration and fibrosis. Wnts play important roles in myogenic progression; however, excessive Wnt signaling is also associated with muscle pathology and muscle aging. Canonical Wnt signals are shown to induce differentiation of myoblasts in vitro and in vivo, although the precise mechanism of this remains unclear.

We have pioneered studies of homeobox factors Barx2 and Pax7 in Wnt-mediated myogenesis, as well as in negative-feedback to attenuate Wnt signalling. This study defines the mechanisms by which canonical Wnt induces myogenesis, the roles of Barx2 and Pax7 in mediating the effects of Wnt signals, and the roles of these factors in controlling Wnt feedback. Our research may help to identify drug or cell-based therapies to increase regeneration and reduce fibrosis.

Our goal is to develop the new strategies that can improve muscle repair.

Molecular mechanisms of lacrimal gland development and regeneration.

The dry eye condition involves chronic lack of ocular surface lubrication; symptoms include inflammation, pain, and in severe cases, blindness. In humans, the lacrimal gland (LG) is the primary contributor to the aqueous layer of the tear film, and dry eye syndrome is typically due to LG malfunction or damage.

Our goal is to develop new therapies able to restore lacrimal gland function. We believe that such therapies could be based on determining factors and mechanisms involved in the regulation of gland morphogenesis and regeneration or on isolation and transplanting stem or progenitor cells. Our ongoing work seeks to identify cell progenitors able to restore the function of the ‘diseased’ lacrimal gland as a critical first step in the development of stem cell-based strategies to treat patients with dry eye conditions. We have recently shown that members of the (FGF) family are important regulators of lacrimal gland homeostasis, regeneration and stem cell function. If we succeed, it would drastically improve the quality of life of people affected by dry eye.

Our long-term goal is to develop therapeutic approaches for the regeneration of damaged human lacrimal gland.